Amphiphilic invertible polymer micelles
Electrochemical impedance spectroscopy (EIS)
Fluorescence lifetime correlation spectroscopy (FLCS)
Microcavity supported lipid bilayer (MSLB)
© 2019 Elsevier Inc. Macromolecules of amphiphilic invertible polymers (AIPs) are capable of self-assembly into micellar assemblies of various morphologies in solvents of different polarities. The micellar assemblies in aqueous media are capable of encapsulating poorly aqueous soluble cargo and can undergo inverse conformational change and cargo release in contact with non-polar media, including potentially, cell membranes. Thus, invertible micellar assemblies have significant potential in drug delivery and related domains. However, to date there have been few investigations into their interactions with lipid membranes. Herein, we investigate the interactions of three recently developed AIPs of varying hydrophobicity/hydrophilicity balance with a highly fluidic microcavity supported 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayer. We combined electrochemical impedance spectroscopy (EIS) with fluorescence correlation spectroscopy (FCS) to understand how the AIP micellar assemblies impacted bilayer permeability and fluidity respectively, across polymer concentrations above and below their critical micelle concentrations (cmcs). At concentration as above their cmcs, all of the AIPs explored increased permeability and decreased the fluidity of the lipid membrane. The extent of impact depended on the hydrophobicity of the AIP. PEG 600 -PTHF 650 , the most hydrophobic of the polymers, synthesized from PEG (molecular weight 600 g/mol) and PTHF (molecular weight 650 g/mol) exerted the greatest influence on the bilayer's physical properties and fluorescence imaging and correlation data indicate that PEG 600 -PTHF 650 micelles loaded with BODIPY probes adsorb and invert at the lipid membrane with release of cargo into the bilayer. This study should help inform future advancement of AIPs for membrane molecular delivery.